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The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson's disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4-12 Hz) spectral power during the period before contralateral leg swing. Furthermore, STN shows increased theta frequency (4-8 Hz) coherence with the primary motor through the initiation and early phase of contralateral leg swing. Additional analysis revealed that each patient had specific frequency bands that could detect a significant difference between left and right initial leg swing. Our findings indicate that there are alternating spectral changes between the two hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both the STN and cortical areas at discrete frequency bands that may be used to drive adaptive DBS to improve gait dysfunction in patients with Parkinson's disease.

BackgroundEpilepsy-associated psychoses are poorly understood, and management is focused on treating epilepsy. Chronic, interictal psychosis that persists despite seizure control is typically treated with antipsychotics. Whether resection of a mesial temporal lobe lesion may improve interictal psychotic symptoms that persist despite seizure control remains unknown.ObservationsIn a 52-year-old man with well-controlled epilepsy and persistent comorbid psychosis, brain magnetic resonance imaging (MRI) revealed an infiltrative, intraaxial, T2 fluid-attenuated inversion recovery intense mass of the left amygdala. The patient received an amygdalectomy for oncological diagnosis and surgical treatment of a presumed low-grade glioma. Pathology was ganglioglioma, World Health Organization grade I. Postoperatively, the patient reported immediate resolution of auditory hallucinations. Patient has remained seizure-free on 2 antiepileptic drugs and no antipsychotic pharmacotherapy and reported lasting improvement in his psychotic symptoms.LessonsThis report discusses improvement of psychosis symptoms after resection of an amygdalar glioma, independent of seizure outcome. This case supports a role of the amygdala in psychopathology and suggests that low-grade gliomas of the limbic system may represent, at minimum, partially reversible etiology of psychotic symptoms.

Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.

IntroductionFreezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.Materials and methodsClinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders.ConclusionDespite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.

Little is known about the electrophysiological activity of the spinal cord during voluntary movement control in humans. We present a novel method for recording electrophysiological activity from the human spinal cord using implanted epidural electrodes during naturalistic movements including overground walking. Spinal electrograms (SEGs) were recorded from epidural electrodes implanted as part of a test trial for patients with chronic pain undergoing evaluation for spinal cord stimulation. Externalized ends of the epidural leads were connected to an external amplifier to capture SEGs. Electromyographic and accelerometry data from the upper and lower extremities were collected using wireless sensors and synchronized to the SEG data. Patients were instructed to perform various arm and leg movements while SEG and kinematic data were collected. This study proves the safety and feasibility of performing epidural spinal recordings from human subjects performing movement tasks.

BackgroundPost-hypoxic myoclonus (PHM) is characterized by generalized myoclonus after hypoxic brain injury. Myoclonus is often functionally impairing and refractory to medical therapies. Deep brain stimulation (DBS) has been used to treat myoclonus-dystonia, but few cases of PHM have been described.Case reportA 33-year-old woman developed severe, refractory generalized myoclonus after cardiopulmonary arrest from drowning. We performed MRI-guided asleep bilateral pallidal DBS placement, resulting in improvement in action myoclonus at one year.DiscussionOur case contributes to growing evidence for DBS for PHM. Interventional MRI guided DBS technique can be used for safe and accurate lead placement.HighlightsWe report a case of a patient who developed post-hypoxic myoclonus after cardiopulmonary arrest from drowning, who later underwent deep brain stimulation to treat refractory myoclonus. This is the first case to describe asleep, interventional MRI-guided technique for implanting DBS leads in post-hypoxic myoclonus.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4–8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements. [ABSTRACT FROM AUTHOR]

BackgroundA majority of patients with insular tumors present with seizures. Although a number of studies have shown that greater extent of resection improves overall patient survival, few studies have documented postoperative seizure control after insular tumor resection.ObjectiveTo (1) characterize seizure control rates in patients undergoing insular tumor resection, (2) identify predictors of seizure control, and (3) evaluate the association between seizure recurrence and tumor progression.MethodsThe study population included adults who had undergone resection of insular gliomas between 1997 and 2015 at our institution. Preoperative seizure characteristics, tumor characteristics, surgical factors, and postoperative seizure outcomes were reviewed.ResultsOne-hundred nine patients with sufficient clinical data were included in the study. At 1 yr after surgery, 74 patients (68%) were seizure free. At final follow-up, 42 patients (39%) were seizure free. Median time to seizure recurrence was 46 mo (95% confidence interval 31-65 mo). Multivariate Cox regression analysis revealed that greater extent of resection (hazard ratio = 0.2899 [0.1129, 0.7973], P = .0127) was a significant predictor of seizure freedom. Of patients who had seizure recurrence and tumor progression, seizure usually recurred within 3 mo prior to tumor progression. Repeat resection offered additional seizure control, as 8 of the 22 patients with recurrent seizures became seizure free after reoperation.ConclusionMaximizing the extent of resection in insular gliomas portends greater seizure freedom after surgery. Seizure recurrence is associated with tumor progression, and repeat operation can provide additional seizure control.

In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13-20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4-8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression.

BackgroundMultiple subpial transections (MST) are a treatment for seizure foci in nonresectable eloquent areas.ObjectiveTo systematically review patient-level data regarding MST.MethodsStudies describing patient-level data for MST procedures were extracted from the Medline and PubMed databases, yielding a synthetic cohort of 212 patients from 34 studies. Data regarding seizure outcome, patient demographics, seizure type, surgery type, and complications were extracted and analyzed.ResultsSeizure freedom was achieved in 55.2% of patients undergoing MST combined with resection, and 23.9% of patients undergoing MST alone. Significant predictors for seizure freedom were a temporal lobe focus (odds ratio 4.9; 95% confidence interval 1.71, 14.3) and resection of portions of the focus, when feasible (odds ratio 3.88; 95% confidence interval 2.02, 7.45). Complications were frequent, with transient mono- or hemiparesis affecting 19.8% of patients, transient dysphasia 12.3%, and permanent paresis or dysphasia in 6.6% and 1.9% of patients, respectively.ConclusionMST is an effective treatment for refractory epilepsy in eloquent cortex, with greater chances of seizure freedom when portions of the focus are resected in tandem with MST. The reported rates of seizure freedom with MST are higher than those of existing neuromodulatory therapies, such as vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, though these latter therapies are supported by randomized-controlled trials, while MST is not. The reported complication rate of MST is higher than that of resection and neuromodulatory therapies. MST remains a viable option for the treatment of eloquent foci, provided a careful risk-benefit analysis is conducted.

Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.

ObjectiveAsymmetric large-amplitude slow activity is sometimes observed on interictal electroencephalography (EEG) in epilepsy. However, few studies have examined slowing during magnetoencephalography (MEG) recordings, which are performed primarily to localize interictal spikes. Also, no prior investigations have compared the sensitivity of MEG to scalp EEG in detecting slow rhythms.MethodsWe performed a retrospective cohort study of focal epilepsy patients who received MEG followed by surgical resection at our institution. We examined MEG, simultaneous EEG, and long-term EEG recordings for prominent asymmetric slow activity (delta-range, 1-4 Hz), and evaluated post-operative seizure outcomes.ResultsWe studied 132 patients with ≥ 1 year post-operative follow-up (mean, 3.6 years). Mean age was 27 (range, 3-68) years, and 55% of patients were male. Asymmetric large-amplitude slow wave activity was observed on interictal MEG in 21 of 132 (16%) patients. Interictal slowing lateralized to the hemisphere of resection in all but one (95%) patient. Among the 21 patients with interictal MEG slowing, 11 (52%) individuals had similarly lateralized EEG slowing, 7 patients had no EEG slowing, and 3 had bilateral symmetric EEG slowing. Meanwhile, none of the 111 patients without lateralized MEG slowing had asymmetric EEG slowing, suggesting significantly higher sensitivity of MEG versus EEG in detecting asymmetric slowing (χ(2)=63.4, p

ObjectivePolymicrogyria (PMG) is a malformation of cortical development characterized by formation of an excessive number of small gyri. Sixty percent to 85% of patients with PMG have epilepsy that is refractory to medication, but surgical options are usually limited. We characterize a cohort of patient with polymicrogyria who underwent epilepsy surgery and document seizure outcomes.MethodsA retrospective study of all patients with PMG who underwent epilepsy surgery (focal seizure foci resection and/or hemispherectomy) at our center was performed by review of all clinical data related to their treatment.ResultsWe identified 12 patients (7 males and 5 female) with mean age of 18 (ranging from 3 months to 44 years) at time of surgery. Mean age at seizure onset was 8 years, with the majority (83%) having childhood onset. Six patients had focal, five had multifocal, and one patient had diffuse PMG. Perisylvian PMG was the most common pattern seen on magnetic resonance imaging (MRI). Eight patients had other cortical malformations including hemimegalencephaly and cortical dysplasia. Scalp electroencephalography (EEG) often showed diffuse epileptic discharges that poorly lateralized but were focal on intracranial electrocorticography (ECoG). Eight patients underwent seizure foci resection and four underwent hemispherectomy. Mean follow-up was 7 years (ranging from one to 19 years). Six patients (50%) were seizure-free at last follow-up. One patient had rare seizures (Engel class II). Three patients were Engel class III, having either decreased seizure frequency or severity, and two patients were Engel class IV. Gross total resection of the PMG cortex trended toward good seizure control.SignificanceOur study shows that even in patients with extensive or bilateral PMG malformations, some may still be good candidates for surgery because the epileptogenic zone may involve only a portion of the malformation. Intracranial ECoG can provide additional localizing information compared to scalp EEG in guiding resection of epileptogenic foci.

Atonic seizures are debilitating and poorly controlled with antiepileptic medications. Two surgical options are primarily used to treat medically refractory atonic seizures: corpus callosotomy (CC) and vagus nerve stimulation (VNS). However, given the uncertainty regarding relative efficacy and surgical complications, the best approach for affected patients is unclear. The PubMed database was queried for all articles describing the treatment of atonic seizures and drop attacks with either corpus callosotomy or VNS. Rates of seizure freedom, >50% reduction in seizure frequency, and complications were compared across the two patient groups. Patients were significantly more likely to achieve a >50% reduction in seizure frequency with CC versus VNS (85.6% versus 57.6%; RR: 1.5; 95% CI: 1.1-2.1). Adverse events were more common with VNS, though typically mild (e.g., 22% hoarseness and voice changes), compared with CC, where the most common complication was the disconnection syndrome (13.2%). Both CC and VNS are well tolerated for the treatment of refractory atonic seizures. Existing studies suggest that CC is potentially more effective than VNS in reducing seizure frequency, though a direct study comparing these techniques is required before a definitive conclusion can be reached.

Invasive electrocorticography (ECoG) is used in patients when it is difficult to localize epileptogenic foci for potential surgical resection. As MR neuroimaging has improved over the past decade, we hypothesized the utilization of ECoG diminishing over time. Using the USA Nationwide Inpatient Sample, we collected demographic and complication data on patients receiving ECoG over the years 1988-2008 and compared this to patients with medically refractory epilepsy during the same time period. A total of 695 cases using extraoperative ECoG were identified, corresponding to 3528 cases nationwide and accounting for 1.1% of patients with refractory epilepsy from 1988-2008. African Americans were less likely to receive ECoG than whites, as were patients with government insurance in comparison to those with private insurance. Large, urban, and academic hospitals were significantly more likely to perform ECoG than smaller, rural, and private practice institutions. The most frequent complication was cerebrospinal fluid leak (11.7%) and only one death was reported from the entire cohort, corresponding to an estimated six patients nationally. Invasive ECoG is a relatively safe procedure offered to a growing number of patients with refractory epilepsy each year. However, these data suggest the presence of demographic disparities in those patients receiving ECoG, possibly reflecting barriers due to race and socioeconomic status. Among patients with nonlocalized seizures, ECoG often represents their only hope for surgical treatment. We therefore must further examine the indications and efficacy of ECoG, and more work must be done to understand if and why ECoG is preferentially performed in select socioeconomic groups.

Objective: Surgical site infection (SSI) is the most common serious complication of deep brain stimulation (DBS) implantation surgery. Here, we report a single-surgeon experience on the efficacy of topical, intrawound vancomycin powder (VP) in reducing SSI for DBS surgery and present the first systematic review and meta-analysis examining the effect of topical vancomycin on SSI in patients after DBS surgery. Methods: For the retrospective review, all unique patients undergoing DBS surgery at UCSF for new hardware implantation or internal pulse generator (IPG) replacement by a single surgeon from September 2013 to March 2019, with at least 1 year of follow-up data, were included. For the meta-analysis, we included all primary studies that compared SSIs with and without application of topical vancomycin in DBS surgeries. Results: 368 unique patients met inclusion criteria; 195 patients received topical VP (VP group) and 173 did not (control). 99/195 patients in the VP group underwent new DBS implantation and 96/195 had IPG replacement. 71/173 patients in the control group had new DBS implantation and 102/173 had IPG replacement. There were 10 total cases of SSI: 4 patients from the VP group (3 new implants and 1 IPG replacement) and 6 patients from the control group (3 new implants and 3 IPG replacements), resulting in SSI rates of 2.1 and 3.5%, respectively (p value = 0.337). Including our retrospective analysis, 6 studies met inclusion criteria for the systematic review and meta-analysis. In the 4 studies that examined primary DBS implants, 479 total patients received topical VP and 436 did not; mean odds ratio for SSI with topical vancomycin was 0.802 (95% confidence interval [CI] 0.175–3.678). Across the 5 studies that examined IPG implantations or replacements, 606 total patients received topical VP while 1,173 patients did not; mean odds ratio for SSI with topical vancomycin was 0.492 (95% CI 0.164–1.475). In either case, topical VP application did not significantly decrease risk of SSI. Conclusion: Surgical infections after DBS surgery are uncommon events, with studies demonstrating mixed results on whether topical vancomycin reduces this risk. Our single-institution retrospective analysis and systematic review of prior studies both demonstrated no significant SSI rate reduction with topical VP. This is likely due to low baseline SSI rates, resulting in a small effect size for prevention. Given the cost-effectiveness, simplicity, and low risk, topical, intrawound VP remains a treatment option to further reduce risk of SSI, particularly in settings with higher baseline infection rates. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is being increasingly utilized to treat movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. An improved understanding of national trends in safety and cost is necessary. Herein, our objectives are to (1) characterize complication, mortality, and cost profiles of patients undergoing DBS for movement disorders in the United States, (2) identify predictors of morbidity and mortality, and (3) evaluate impact of complications on cost. DBS surgeries were extracted from the National Inpatient Sample (NIS) 2002–2014 for the clinical indications of PD, ET, and dystonia. Patient characteristics and eight complication categories (hardware malfunction, infection, neurological, other haemorrhagic, thromboembolic, cardiac, pulmonary, and renal/urinary) were reviewed. Outcomes included complications, mortality, hospitalization length, and inflation-adjusted cost. There were 44,866 weighted admissions (PD-73.5%, ET-22.7%, dystonia-3.8%). The number of procedures increased 2.22-fold from 2002 to 2014 (N = 2372 in 2002; N = 5260 in 2014). Inpatient cost was $22,802 ± 13,164, remaining stable from 2002 to 2014 ($24,188 ± 15,910, $20,630 ± 11,031, respectively). Four percent experienced complications (dystonia-6.0%, PD-4.4%, ET-3.1%, p <.001). In-hospital mortality was 0.2%. Cost was greater in patients with complications ($36,306 ± 29,263 vs. $22,196 ± 11,560, p <.001). Most common complications were renal/urinary (1.5%), neurological (1.1%), and pulmonary (0.7%). Thromboembolic, pulmonary, and haemorrhagic complications were associated with greatest cost. Increased DBS utilization for adult movement disorders in the United States from 2002 to 2014 was attributed to rapid adoption by teaching hospitals for PD. DBS remains a safe procedure with low overall complications and stable inpatient costs from 2002 to 2014. Complication risks vary by type of movement disorder, and although rare, multiple complications increase morbidity and cost of care. [ABSTRACT FROM AUTHOR]